PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Edited RNA + invasive DNA add individuality

2013-11-08
(Press-News.org) Contact information: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Edited RNA + invasive DNA add individuality

PROVIDENCE, R.I. [Brown University] — The story of why we are all so different goes well beyond the endless mixing and matching of DNA through breeding. A new study in the journal Nature Communications, for instance, reports a new molecular mechanism of individual variation found in fruit flies that uses components operating in a wide variety of species, including humans.

The new mechanism is based in a surprising genetic oddity. Nearly all genomes — those of humans, fruit flies, and even corn and rice — are constantly grappling with parasitic snippets of genetic material called "transposons." These snippets copy themselves, move around, and embed themselves within DNA. If left unchecked, transposons can alter how genetic instructions are carried out in the body,usually for the worse, sometimes for the better. But genomes don't leave transposons unchecked. They "look" for tell-tale double-stranded RNA associated with the transposons, chop the strands up and use the pieces to "silence" the invaders.

In the new paper, scientists show that an enzyme called ADAR, which edits RNA in humans, flies, and many other creatures, edits double-stranded RNAs. This loosens the system that keeps "Hoppel" transposons silenced in fruit flies. When transposons are silenced, it's done by keeping them locked tight around tiny balls of material called chromatin.

Since the amount of ADAR varies from one individual to the next, the amount of jailbreaking from those chromatin prison varies too, and that should lead to altered gene expression. After showing that an abundance of ADAR reduces silencing of a common transposon in the flies — and that a lack of ADAR meant widespread silencing — the researchers measured two consequences of different levels of ADAR activity: a 20-percent difference in life span and difference in eye color (red rather than white).

The study was focused on fruit flies, ADAR, and the double-stranded RNA of the Hoppel transposon, but the ability of RNA editors to loosen the silencing of at least some transposons may be a source of individual variation in humans and other species too, said Brown University biologist Robert Reenan, senior author of the new study published online. Editing of double-stranded RNA — or a lack of editing — has already been linked to diseases in people, including amyloid lateral sclerosis and, specifically in the case of ADAR, Aicardi-Goutières syndrome.

"ADAR in humans functions the same way it does in flies, and double-stranded RNAs are made in humans the same way," said Reenan, professor of biology in the Department of Molecular Biology, Cell Biology and Biochemistry. "They are all generic, off the shelf staples of the biological toolkit. This is not anything that is particular to flies."

Picking the double strand

Many of Reenan's studies focus on ADAR's editing activity in the development of the nervous system, but this investigation began years ago when lead author and then graduate student Yiannis Savva happened to overexpress ADAR in fruit fly salivary gland cells. He found some bound in an unexpected place: one specific site on chromosome four.

Reenan recalled: "I told him that's either an artifact or it will be the centerpiece of your thesis."

Various tests revealed that the chromosome four site was a home for several Hoppel transposons making a double-stranded RNA.

Savva and Reenan were curious about what business ADAR had with the transposon. A series of experiments in ensuing years did just that. They relocated the transposons to places where they weren't and found that ADAR followed. They deleted the double-stranded RNA from chromosome four and found that ADAR was no longer there. They identified specific editing sites and signs of editing on the double stranded RNA.

Savva and his collaborators then measured silencing of tranposons with varying levels of ADAR and found that the more ADAR there was, the less silencing there was.

Then, working with Stephen Helfand, an expert on the biology of aging, they noticed that a reduction of editing increases life span.

"As a loss of silencing has been associated with aging in Drosophila and other organisms, we performed lifespan analyses on [low-ADAR] adults and wild-type controls and found a ~20-percent increase in the median life span of [low-ADAR] males and females," the authors wrote in Nature Communications.

Look in their eyes

Later they looked at eye color, using natural (wild-type) flies and those where ADAR activity was either artificially hamstrung or excessively active. The natural flies have eyes that run a full continuum from red to white with various "variegating" blends in between that reflect the silencing state of their eye color gene. In the excessively ADAR-active flies there was little silencing and eyes turned out red much more often than normal. In the ADAR-hamstrug flies, virtually all of the eyes were white (reflecting a lot of silencing of the red color gene).

Ultimately, Savva said, ADAR appears to be allowing transposons like Hoppel to exercise their capacity to regulate gene expression, even though they are really just uninvited guests in the genome.

"What ADAR does is fine tune this regulatory network," Savva said. "In cells where you have ADAR, the network is activated. In cells where you don't it's silenced. It provides dynamicity."

In other words, some of the differences among us may be apparent in the eyes of flies.



INFORMATION:

In addition to Savva, Reenan, and Helfand, authors on the paper are James Jepson, Yoah-Jen Chang, Rachel Whitaker, Brian Jones, Nian Jiang, and Guyu Du of Brown; Georges St. Laurent of Brown and the St. Laurent Institute; and Michael Tackett and Phillipp Kapranov of the St. Laurent Institute.

The National Institute on Aging (grants: AG16667, AG24353, AG25277) and the Ellison Medial Foundation funded the research.



ELSE PRESS RELEASES FROM THIS DATE:

Defending food crops: Whitefly experimentation to prevent contamination of agriculture

2013-11-08
Defending food crops: Whitefly experimentation to prevent contamination of agriculture VIDEO: On November 8th, JoVE, the Journal of Visualized Experiments, ...

CNIO scientists decipher how the immune system induces liver damage during hepatitis

2013-11-08
CNIO scientists decipher how the immune system induces liver damage during hepatitis The immune system causes liver damage when the organ becomes inflamed by the JunB gene, a member of the AP-1 complex Viral infections are the primary cause of ...

Researchers uncover origins of cattle farming in China

2013-11-08
Researchers uncover origins of cattle farming in China An international team of researchers, co-led by scientists at the University of York and Yunnan Normal University, has produced the first multi-disciplinary evidence for management of cattle populations in ...

TGen-led study reveals TWEAK-Fn14 as key drug target

2013-11-08
TGen-led study reveals TWEAK-Fn14 as key drug target Next steps: Drug development and clinical trials that could benefit patients PHOENIX, Ariz. — Nov. 8, 2013 — A cellular pathway interaction known as TWEAK-Fn14, often associated with repair ...

Volunteers join scientists in finding out who gets rid of cow dung

2013-11-08
Volunteers join scientists in finding out who gets rid of cow dung With more than a billion cows around the world, an immense amount of dung is produced each day. Most of these droppings will evidently disappear, as the world is still green rather than brown. Now a team ...

Gut hormone test predicts individual efficacy of gastric bypass

2013-11-08
Gut hormone test predicts individual efficacy of gastric bypass The gastric bypass is one of the most commonly performed surgical procedures in the treatment of obesity. In most patients, ...

A*STAR scientists uncover potential drug target to nip cancer in the bud

2013-11-08
A*STAR scientists uncover potential drug target to nip cancer in the bud This discovery could eradicate cancers more effectively and prevent relapses 1. Scientists at A*STAR have discovered an enzyme, Wip1 phosphatase, ...

Novel LEDs pave the way to cheaper displays

2013-11-08
Novel LEDs pave the way to cheaper displays Applications in smart phones or luminescent bathroom tiles conceivable / Collaboration of Bonn University, Regensburg University, the University of Utah and MIT OLEDs are already used in the displays of smart phones ...

New test for patients with sore throats cuts antibiotic use by nearly a third

2013-11-08
New test for patients with sore throats cuts antibiotic use by nearly a third A new 'clinical score' test for patients with sore throats could reduce the amount of antibiotics prescribed and result in patients feeling better more quickly, research in the British ...

Mother's immunosuppressive medications not likely to put fetus at risk

2013-11-08
Mother's immunosuppressive medications not likely to put fetus at risk Women with chronic autoimmune diseases who take immunosuppressive medications during their first trimester of pregnancy are not putting their babies at significantly increased ...

LAST 30 PRESS RELEASES:

Study confirms that people with ADHD can be more creative. The reason may be that they let their mind wander

Research gives insight into effect of neurodegenerative diseases on speech rhythm

Biochar and plants join forces to clean up polluted soils and boost ecosystem recovery

Salk scientist Joseph Ecker awarded McClintock Prize for Plant Genetics and Genome Studies

ADHD: Women are diagnosed five years later than men, despite symptoms appearing at the same age.

Power plants may emit more pollution during government shutdowns

Increasing pressures for conformity de-skilling and demotivating teachers, study warns

Researchers develop smarter menstrual product with potential for wearable health monitoring

Microwaves for energy-efficient chemical reactions

MXene current collectors could reduce size, improve recyclability of Li-ion batteries

Living near toxic sites linked to aggressive breast cancer

New discovery could open door to male birth control

Wirth elected Fellow of American Physical Society

The Journal of Nuclear Medicine Ahead-of-Print Tip Sheet: October 10, 2025

Destined to melt

Attitudes, not income, drive energy savings at home

The playbook for perfect polaritons

‘Disease in a dish’ study of progressive MS finds critical role for unusual type of brain cell

Solar-powered method lights the way to a ‘de-fossilized’ chemical industry

Screen time linked to lower academic achievement among Ontario elementary students

One-year outcomes after traumatic brain injury and early extracranial surgery in the TRACK-TBI Study

Enduring outcomes of COVID-19 work absences on the US labor market

Affirmative action repeal and racial and ethnic diversity in us medical school admissions

Cancer progression illuminated by new multi-omics tool

Screen time and standardized academic achievement tests in elementary school

GLP-1RA order fills and out-of-pocket costs by race, ethnicity, and indication

Study finds HEPA purifiers alone may not be enough to reduce viral exposure in schools

UVA Health developing way to ID people at risk of dangerous lung scarring even before symptoms appear

How can we know when curing cancer causes myocarditis?

Male infertility in Indian men linked to lifestyle choices and hormonal imbalances

[Press-News.org] Edited RNA + invasive DNA add individuality